This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diarrhea affects approximately 4 billion people per year worldwide with number of deaths estimated to be around 2 million. Escherichia coli (E. coli) that attach to the surface of the intestinal lining and cause its destruction, are common causes for infectious diarrhea worldwide, especially in children less than 2 years of age. Since E. coli does not cause clinical illness in mice, Citrobacter rodentium a bacteria that causes natural disease in mice with clinical progression of illness that closely resembles human E. coli infections;is used as an in-vivo model. As in humans, the susceptibility of mice to these bacteria is dependent of age group (the young more severely affected than the adults), and genetic background. Many studies in mice have shown that the immune status has minimal effect on the severity or course of the disease. Our study is aimed at understanding the role of epithelial cell lining of the intestines in defining the severity and course of disease. Epithelial cells are ideal target, since they not only provide a physical barrier in the intestine, but also actively part-take in controlling the local resistance to infectious agents. We will evaluate structural and functional changes in epithelial cells following infection with C. rodentium, and the results will help us understand the role of epithelial cells in determining the susceptibility and severity of bacterial diarrheal illnesses of humans and animals.